1. Field of the Invention
The invention generally relates to a vaccine for human hookworm. In particular, the invention provides a human hookworm vaccine comprising an L3 larval stage antigen (e.g. Na-ASP-2 or Na-SAA-2) and at least one adult stage human hookworm antigen (e.g. Na-APR-1, Na-CP-2, Na-CP-3, Na-CP-4, Na-CP-5, or Na-GST-1) and two or more adjuvants, one of which is an aluminum-based adjuvant such as Alhydrogel®.
2. Background of the Invention
Hookworms are gastrointestinal nematodes that infect approximately 600 million people in developing countries (Hotez et al, 2006a). Adult hookworms bury their heads beneath the mucosa of the human intestine and feed on blood. Moderate to heavy infections result in iron deficiency anaemia, the major pathologic sequella of hookworm disease, as well as protein malnutrition. The resulting hookworm disease and anemia has a serious deleterious impact on many aspects of the health of infected individuals, including childhood growth retardation and cognitive development, and impaired fetal development during pregnancy (Hotez et al, 2004). The global disease burden resulting from chronic hookworm infection in childhood and pregnancy is enormous, possibly as high as 22 million disability-adjusted life years annually (Chan, 1997), making hookworm the second most important parasitic infection of humans after malaria (Hotez et al, 2005). In addition, the chronic immune suppression induced by hookworms and other helminths also has enormous impact on the ability of people to respond in a competent fashion to other infections (including malaria and HIV/AIDS and vaccines (Elliott et al, 2005; Su et al. 2005; Cooper et al., 2001; Cooper et al., 1999; Hotez et al, 2006b).
Unlike many other human helminthiases, clear-cut immunity against hookworms does not develop in the majority of infected individuals (Loukas et al., 2005). Indeed, the oldest people living in an endemic community sometimes have the heaviest worm burdens (Bethony et al., 2002). While anthelminthic drugs of the benzimidazole class are highly effective at eliminating existing hookworm infections, they do not protect against rapid re-infection (Hotez et al, 2006a). In areas of high transmission, hookworm re-infection will occur within 4-12 months (Albonico et al, 1995), leading to concerns about the long-term sustainability of such practices (Kremer 2004). In addition, newer data indicates that the efficacy of benzimidazole drugs decreases with frequent use (Albonico et al, 2003), leading to concerns about the possibility that anthelminthic drug resistance has developed (Albonico et al, 2004; Bethony et al, 2006). These observations have led to calls by the World Health Organization and other international agencies to develop new tools for the control of hookworm, including a hookworm vaccine (WHO, 2005). Therefore, an anthelminthic vaccine that induces immunological protection to minimize pathology and interrupt hookworm transmission is a highly desirable goal.
While regional economic growth (and with it, improvements in sanitation and clean water) in some parts of North America, Japan, South Korea, and China have translated into substantial reductions in endemic hookworm (Hotez et al, 2006a), estimated prevalence rates for the world's poorest and least developed regions remain high. For example, infection rates in sub-Saharan Africa (SSA) are equivalent to those first estimated more than 60 years ago (DeSilver et al., 2003), where an estimated 198 million cases occur (DeSilva et al, 2003). High hookworm infestation rates are principally in poverty-stricken rural areas where access to medical care is severely limited. Widespread use of a hookworm vaccine would lead to significant improvement in global health and in economic development (Hotez et al, 2006a; Hotez and Ferris, 2006). Therefore, an ideal vaccine hookworm vaccine would also be relatively easy and inexpensive to produce, and would be effective without the need for constant boosting.
The prior art has thus far failed to provide such a vaccine against human hookworm.